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Arterioscler Thromb Vasc Biol. 2019 Apr;39(4):704-718. doi: 10.1161/ATVBAHA.118.311992.

Transthoracic Pulmonary Artery Denervation for Pulmonary Arterial Hypertension.

Author information

1
From the State Key Laboratory of Cardiovascular Diseases and Center for Pediatric Cardiac Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases (Y.H., Y.-W.L., X.-L.Z., J.L., L.X., J.M., P.-H.W., H.Z.), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing.
2
Children's Heart Center, the Second Affiliated Hospital and Yuying Children's Hospital, Institute of Cardiovascular Development and Translational Medicine, Wenzhou Medical University, Zhejiang, China (H.-Z.P.).
3
Institute of Basic Medical Sciences (J.Y.), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing.
4
Key Laboratory of Pulmonary Vascular Medicine, Fuwai Hospital, National Center for Cardiovascular Diseases (Z.-C.J.), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing.
5
Heart Center and Shanghai Institution of Pediatric Congenital Heart Diseases, Shanghai Children's Medical Center, National Children's Medical Center, Shanghai Jiao Tong University School of Medicine, China (H.Z.).

Abstract

Objective- Pulmonary arterial hypertension is characterized by progressive pulmonary vascular remodeling and persistently elevated mean pulmonary artery pressures and pulmonary vascular resistance. We aimed to investigate whether transthoracic pulmonary artery denervation (TPADN) attenuated pulmonary artery (PA) remodeling, improved right ventricular (RV) function, and affected underlying mechanisms. We also explored the distributions of sympathetic nerves (SNs) around human PAs for clinical translation. Approach and Results- We identified numerous SNs in adipose and connective tissues around the main PA trunks and bifurcations in male Sprague Dawley rats, which were verified in samples from human heart transplant patients. Pulmonary arterial hypertensive rats were randomized into TPADN and sham groups. In the TPADN group, SNs around the PA trunk and bifurcation were completely and accurately removed under direct visualization. The sham group underwent thoracotomy. Hemodynamics, RV function, and pathological changes in PA and RV tissues were measured via right heart catheterization, cardiac magnetic resonance imaging, and pathological staining, respectively. Compared with the sham group, the TPADN group had lower mean pulmonary arterial pressures, less PA and RV remodeling, and improved RV function. Furthermore, TPADN inhibited neurohormonal overactivation of the sympathetic nervous system and renin-angiotensin-aldosterone system and regulated abnormal expressions and signaling of neurohormone receptors in local tissues. Conclusions- There are numerous SNs around the rat and human main PA trunks and bifurcations. TPADN completely and accurately removed the main SNs around PAs and attenuated pulmonary arterial hypertensive progression by inhibiting excessive activation of the sympathetic nervous system and renin-angiotensin-aldosterone system neurohormone-receptor axes.

KEYWORDS:

denervation; pulmonary artery; pulmonary hypertension; renin-angiotensin-aldosterone system; sympathetic nervous system

PMID:
30816802
DOI:
10.1161/ATVBAHA.118.311992

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